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. 2017 Feb 9;101(6):791–802. doi: 10.1002/cpt.589

Table 1.

Summary of genomewide association study of antiplatelet effects and pharmacokinetic of clopidogrel in stage I and replication results of pharmacokinetic in stage II

SNP CHR Gene symbol P value (n = 115) in stage I P value (n = 31) in stage IIa P value (n = 32) in stage IIb
PRU >208 PRU H4 C2h Clop Tmax Clop Cmax Clop AUC0‐4h H4 Tmax H4 Cmax H4 AUC0‐4h
rs74460025 5 GABRB2 2.61 × 10‐5 5.08 × 10‐3 5.19 × 10‐3 0.679 0.973 0.672 0.760 0.740 0.668 0.9402
rs17145154 7 DNAH11 4.72 × 10‐5 6.36 × 10‐4 2.40 × 10‐2 0.672 0.557 0.799 0.0513 0.950 0.794 0.4269
rs4741806 9 Intergenic 4.04 × 10‐4 6.28 × 10‐5 2.40 × 10‐3 0.972 0.483 0.544 0.495 0.918 0.541 0.9502
rs1048196 10 HELLS 1.45 × 10‐5 4.05 × 10‐5 4.20 × 10‐4 0.978 0.402 0.587 0.742 0.248 0.0273 0.0135
rs1926711 10 CYP2C18 8.24 × 10‐6 3.51 × 10‐5 6.61 × 10‐3 0.667 0.153 0.291 0.773 0.517 0.0843 0.0153
rs4244285 10 CYP2C19 1.66 × 10‐5 6.01 × 10‐5 2.20 × 10‐4 0.955 0.125 0.205 0.842 0.172 0.00861 0.0334
rs2852213 11 GRIK4 8.77 × 10‐5 5.12 × 10‐3 1.62 × 10‐2 0.593 0.147 0.0794 0.121 0.679 0.495 0.9842
rs774392 12 GRIP1 2.49 × 10‐5 3.18 × 10‐4 6.72 × 10‐3 0.432 0.444 0.369 0.382 0.611 0.387 0.961
rs12913988 15 ATP10A 1.57 × 10‐3 9.69 × 10‐6 1.47 × 10‐2 0.307 0.831 0.691 0.895 0.538 0.617 0.9948
rs12456693 18 SLC14A2 6.83 × 10‐5 1.07 × 10‐2 8.52 × 10‐3 0.00485 0.262 0.172 0.0444 0.0245 0.129 0.4131
rs1571678 21 N6AMT1 1.21 × 10‐3 2.65 × 10‐5 6.85 × 10‐3 0.0249 0.969 0.958 0.0551 0.286 0.358 0.0643
rs2254638 21 N6AMT1 1.87 × 10‐3 5.37 × 10‐5 6.29 × 10‐3 0.0249 0.969 0.958 0.0551 0.286 0.358 0.0386
rs17209532 22 Intergenic 2.46 × 10‐3 1.92 × 10‐5 3.08 × 10‐2 0.218 0.266 0.167 0.0670 0.520 0.306 0.7581
rs7292279 22 Intergenic 7.39 × 10‐4 4.34 × 10‐5 9.08 × 10‐3 0.730 0.689 0.863 0.385 0.944 0.860 0.1483
rs13123057 4 UGT2B11 8.69 × 10‐3 8.94 × 10‐3 8.69 × 10‐4 0.334 0.984 0.847 0.332 0.396 0.850 0.7324
rs12369968 12 MGST1 3.43 × 10‐4 3.57 × 10‐3 9.18 × 10‐4 0.459 0.440 0.448 0.131 0.0904 0.135 0.9919
rs2487032 9 ABCA1 3.46 × 10‐3 3.75 × 10‐2 5.34 × 10‐3 0.243 0.0211 0.00590 0.0189 0.382 0.329 0.8812
rs4147820 1 ABCA4 1.74 × 10‐3 8.42 × 10‐4 7.00 × 10‐3 0.495 0.448 0.604 0.759 0.673 0.679 0.662

AUC, area under the curve; Clop, clopidogrel; Cmax, peak plasma concentration; PRU, P2Y12 reaction unit; SNP, single‐nucleotide polymorphism; Tmax, time of maximum plasma concentration.

SNPs were associated with PRU or PRU >208 (P < 1 × 10−4) and CH4 at 2 h (P < 0.01), or SNPs in absorption, distribution, metabolism, and excretion gene were associated with PRU or PRU >208 (P < 0.05) and CH4 (P < 0.01) in stage I.

SNPs in bold indicate associations with pharmacokinetic parameters of clopidogrel or its active metabolite H4 in stage IIa.